Study of the viral, genetic and immunologic characteristics of human host on the development of asymptomatic and severe clinical manifestations of dengue

Abstract

Dengue fever results from infection by any of the dengue virus (DENV), and it is considered the main arbovirus infection worldwide, and an extremely important one for our country. Dengue has a wide variety of clinical symptoms, ranging from asymptomatic infections to severe forms called dengue hemorrhagic fever / dengue shock syndrome (DHF / DSS). The pathogenesis of dengue infections, and particularly the severe presentations, is complex, including the involvement of the immune response in both protection and development of severe forms and having the viral and host characteristics as an adjunct in the pathogenesis of severe forms. It is extremely important to understand the molecular and immunological basis of pathogenesis of dengue to assist in the treatment and prevention of this disease, facilitate the development of vaccines that protect against all four serotypes of DENV in such a way they do not increase the severity of disease due to the effect of "antibody-enhancement of the disease". This project aims to evaluate various parameters related to the pathogenesis of dengue, in vivo and in vitro, in order to make the correlation of the different presentations of the disease with genetics, host immune response and the virulence of the strains, assessing the relative importance of each of these factors in the development of more severe forms of disease. Viral and patient's personal characteristics (genetic and immunological) will be evaluated, as well as the cells present in the serum of patients with dengue fever, dengue with complications, dengue hemorrhagic fever and dengue asymptomatic infection. The study of this last group is of extreme importance and has never been evaluated by any research group. Citokine expression will be investigated by a new technique that has not been used to study dengue. We expect that this project will contribute to a better understanding of host response triggered by virus infection, which will assist in developing vaccines and treatments for dengue. (AU)